Retrospective survey of urea cycle disorders: Part 1. Clinical and laboratory observations of thirty‐two Japanese male patients with ornithine transcarbamylase deficiency

Abstract

In a retrospective survey done from 1978-1988 in Japan, 32 male patients with ornithine transcarbamylase (OTC) deficiency were identified. We classified a neonatal and 2 late-onset groups, depending on clinical manifestations and the age at onset; group 1 (0-28 days; N = 10), group 2 (29 days-5 years; N = 13), and group 3 (greater than 5 years; N = 9). Compared to findings in the group 2 patients, there was a higher rate of mortality and a higher incidence of mental retardation in association with a great decrease in enzyme activity in group 1. In group 3, the mortality rate and enzyme activities were similar to those in group 1. However, patients in this group were asymptomatic prior to the first episode. Enzyme activities were measured mostly in autopsy samples. The serum citrulline levels (enzyme product) were highest in this group. Thus, the mutant enzymes were apparently labile with greater activities in vivo than in vitro. Treatments, including a protein-restricted diet, arginine supplementation, and sodium benzoate administration, resulted in a favorable prognosis for survivors with partial enzyme deficiency. We wish to emphasize that the incidence of late onset of this disease is higher than heretofore considered.

İnspiratuvar stridor klinik bulgusu ile saptanan argininosüksinik asidüri: yenidoğan olgusu

“…However, the most frequently seen side effects of this treatment include nausea, vomiting and irritability (6). Since infections can proceed rapidly in cases with a diagnosis of argininosuccinic aciduria, early hospitalization and use of IV antibiotics will significantly prevent deaths due to infections in these infants (2). Treatment of our case was adjusted as 1.5 g/kg/day protein and 0.5 g/kg/day L-arginine.…”

“…Arginine is the most important essential amino acid affecting production negatively in argininosuccinic aciduria and therefore its deficiency should absolutely be compensated (10). For this objective, 1.2-2 g/kg/day protein diet containing 0.4-0.7 g/kg/day L-arginine should be given to the patients (2,6). While the initial dose of sodium benzoate is 250 mg/kg/day, in severe cases the dose can be increased up to 500 mg/kg/day.…”

“…The third form is the subacute or lateonset type and signs occur in infancy, childhood or puberte. The most prominent characteristics of the lateonset type include mental retardation, intermittent ataxia and intermittent hyperammonemia (2). This article presents a case diagnosed with argininosuccinic aciduria in the neonatal period with a clinical sign of severe stridor.…”

“…Due to enzyme deficiency argininosuccinic acid (ASA) and ammonia accumulate in body fluids (1). The deficiency was firstly defined in 1958 by Allan et al (2). Its incidence has been reported to be 1/70 000-91 000 (3).…”

Ten novel mutations of the ornithine transcarbamylase (OTC) gene in OTC deficiency

“…The phenotype of male hemizygotes is classified into two groups; one belongs to the neonatal onset group, (within 1 month of age) and the other is of late onset. Female heterozygotes have symptoms ranging from symptomatic to mild or severe, depending on lyonization (Brusilow and Horwich, 1995;Matsuda et al, 1991;Nagata et al, 1991). It is presumed that one-third of the mutations are due to de novo events, and most of these mutations are likely to arise in the paternal germ cell (Tuchman et al, 1995).…”